MSACL 2024 Abstract

An Extraordinarily High Bromazolam Concentration in a Clinical Case

Donna Papsun, Kris Graf, Brittany K. Casey
NMS Labs

Brittany Casey, Ph.D. (Presenter) NMS Labs >> POSTER (PDF)

Presenter Bio: Dr. Brittany Casey joined NMS labs in 2023; prior to that she was the Chief of Forensic Chemistry for the Dallas County Southwestern Institute of Forensic Sciences and oversaw the Toxicology (postmortem, DWI/DUID, and DFC), Breath Alcohol, and Controlled Substances sections of the Institute. An integral part of her work there was directing the design, validation, and implementation of new methodology in the Toxicology and Controlled Substances sections. She also held an appointed assistant professor position at the University of Texas Southwestern Medical School. Originally from North Texas, she completed her undergraduate studies in biochemistry at Baylor University in Waco, Texas, and participated in undergraduate research studying tissue bonding and meniscal repair using substituted napthalimides. She earned her doctoral degree in chemistry from Tulane University in New Orleans, Louisiana, where her research focused on the synthesis and characterization of dendritic mass spectral calibrants and transdermal drug carriers. Brittany is a fellow of the American Board of Forensic Toxicology and is active in professional organizations such as the Society of Forensic Toxicologists (SOFT) and the American Society for Mass Spectrometry (ASMS). She also holds a Texas Forensic Analyst License in the category of Toxicology (Interpretive).

Relevant Financial Disclosures (within past 24 months, reported on Mar 19, 2024) Salary NMS Labs Conflict mitigation NOT REQUIRED.

Case Description:
A 42-year-old male presented at a medical facility following possible drug overdose. Toxicology testing was performed and targeted commonly encountered drugs and metabolites such as amphetamines, anticonvulsants, antidepressants, antihistamines, antipsychotics, benzodiazepines, central nervous system stimulants, hallucinogens, hypnosedatives, muscle relaxants, and non-steroidal anti-inflammatory agents, in addition to a number of novel psychoactive substances (NPS). Bromazolam was identified and quantitated as part of the confirmation testing in this case.

Background:
Bromazolam was first synthesized in 1976 but was never approved for use. Today it is frequently found in conjunction with opioids such as such as fentanyl and heroin, often in the form of clandestine or counterfeit tablets. It is an increasingly prevalent NPS, as evidenced by an increase in identifications in both seized drugs and toxicology samples. Bromazolam use is generally characterized by central nervous system depression and can be life-threatening; therefore, accurate identification and quantitation of bromazolam is critical for patient care. Toxicology screening via immunoassay is common and would likely yield a presumptive positive result for benzodiazepines as a drug class but would not allow for identification of the analyte of interest. The use of powerful mass spectral techniques like TOF coupled with a comprehensive and relevant scope of analysis make it possible to efficiently and effectively test for NPS in clinical samples.

MS Method and Results:
Routine screening for THC, barbiturates, salicylate, and gabapentin was performed via immunoassay. For expanded screening, 0.5 mL of serum was buffered, extracted with organic solvent, and analyzed via LC-TOF-MS. Bromazolam confirmation testing utilized 0.5 mL of buffered serum in a liquid/liquid extraction. The reconstituted extract was separated using UPLC and analyzed with positive-ion electrospray tandem mass spectrometry for detection and quantitation. The patient’s serum bromazolam concentration was 1400 ng/mL.

Discussion and Conclusion:
Seizures, hyperthermia, and myocardial injury associated with bromazolam use were recently reported, and deaths attributed to bromazolam use are increasing. Bromazolam use can have serious and life-threating impacts on patient health, and its inclusion in clandestine or counterfeit tablets complicates patient care, as patients are often unaware of the true composition of these items. Previous reports of bromazolam-positive samples, including fatalities, were one to two orders of magnitude lower in concentration than the case reported herein.